排序方式: 共有37条查询结果,搜索用时 62 毫秒
31.
The STING pathway and regulation of innate immune signaling in response to DNA pathogens 总被引:1,自引:1,他引:0
The innate immune system has evolved a variety of sensing mechanisms to detect and counter microbial invasion. These include
the Toll-like receptor (TLR), cytoplasmic, nucleotide binding oligomerization domain (NOD)-like receptor and RIG-I-like helicase
(RLH) pathways. However, how the cell detects pathogen-associated DNA to trigger host defense, including the production of
interferon, remains to be fully clarified. Understanding these processes could have profound implications into how we understand
and treat a variety of microbial-related disease, including viral-associated cancers, as well as autoimmune disorders. Recently,
an endoplasmic reticulum-associated molecule referred to as STING (for stimulator of interferon genes) was isolated and shown
to be critical for regulating the production of IFN in response to cytoplasmic DNA. Here, we review recent discoveries relating
to the detection of foreign DNA, including the importance of the STING and inflammasome pathways and the triggering of innate
signaling processes. 相似文献
32.
SH Lee AC Kwan S Zhang V Phoumthipphavong JG Flannery SC Masmanidis H Taniguchi ZJ Huang F Zhang ES Boyden K Deisseroth Y Dan 《Nature》2012,488(7411):379-383
Inhibitory interneurons are essential components of the neural circuits underlying various brain functions. In the neocortex, a large diversity of GABA (γ-aminobutyric acid) interneurons has been identified on the basis of their morphology, molecular markers, biophysical properties and innervation pattern. However, how the activity of each subtype of interneurons contributes to sensory processing remains unclear. Here we show that optogenetic activation of parvalbumin-positive (PV+) interneurons in the mouse primary visual cortex (V1) sharpens neuronal feature selectivity and improves perceptual discrimination. Using multichannel recording with silicon probes and channelrhodopsin-2 (ChR2)-mediated optical activation, we found that increased spiking of PV+ interneurons markedly sharpened orientation tuning and enhanced direction selectivity of nearby neurons. These effects were caused by the activation of inhibitory neurons rather than a decreased spiking of excitatory neurons, as archaerhodopsin-3 (Arch)-mediated optical silencing of calcium/calmodulin-dependent protein kinase IIα (CAMKIIα)-positive excitatory neurons caused no significant change in V1 stimulus selectivity. Moreover, the improved selectivity specifically required PV+ neuron activation, as activating somatostatin or vasointestinal peptide interneurons had no significant effect. Notably, PV+ neuron activation in awake mice caused a significant improvement in their orientation discrimination, mirroring the sharpened V1 orientation tuning. Together, these results provide the first demonstration that visual coding and perception can be improved by increased spiking of a specific subtype of cortical inhibitory interneurons. 相似文献
33.
H Pälike MW Lyle H Nishi I Raffi A Ridgwell K Gamage A Klaus G Acton L Anderson J Backman J Baldauf C Beltran SM Bohaty P Bown W Busch JE Channell CO Chun M Delaney P Dewangan T Dunkley Jones KM Edgar H Evans P Fitch GL Foster N Gussone H Hasegawa EC Hathorne H Hayashi JO Herrle A Holbourn S Hovan K Hyeong K Iijima T Ito S Kamikuri K Kimoto J Kuroda L Leon-Rodriguez A Malinverno TC Moore BH Murphy DP Murphy H Nakamura K Ogane C Ohneiser C Richter R Robinson EJ Rohling O Romero K Sawada H Scher 《Nature》2012,488(7413):609-614
Atmospheric carbon dioxide concentrations and climate are regulated on geological timescales by the balance between carbon input from volcanic and metamorphic outgassing and its removal by weathering feedbacks; these feedbacks involve the erosion of silicate rocks and organic-carbon-bearing rocks. The integrated effect of these processes is reflected in the calcium carbonate compensation depth, which is the oceanic depth at which calcium carbonate is dissolved. Here we present a carbonate accumulation record that covers the past 53 million years from a depth transect in the equatorial Pacific Ocean. The carbonate compensation depth tracks long-term ocean cooling, deepening from 3.0-3.5?kilometres during the early Cenozoic (approximately 55?million years ago) to 4.6 kilometres at present, consistent with an overall Cenozoic increase in weathering. We find large superimposed fluctuations in carbonate compensation depth during the middle and late Eocene. Using Earth system models, we identify changes in weathering and the mode of organic-carbon delivery as two key processes to explain these large-scale Eocene fluctuations of the carbonate compensation depth. 相似文献
34.
Gerardo Rodriguez-Araujo Hironori Nakagami Hiroki Hayashi Masaki Mori Tetsuya Shiuchi Yasuhiko Minokoshi Yoshikazu Nakaoka Yoichi Takami Issei Komuro Ryuichi Morishita Yasufumi Kaneda 《Cellular and molecular life sciences : CMLS》2013,70(6):1123-1133
Insulin is the main glucoregulator that promotes the uptake of glucose by tissues and the subsequent utilization of glucose as an energy source. In this paper, we describe a novel glucoregulator, the alpha-synuclein (SNCA) protein, that has previously been linked to Parkinson’s disease. Treatment with recombinant SNCA promotes glucose uptake in vitro in preadipocytes and in vivo in the adipose tissues and skeletal muscles of mice through the LPAR2/Gab1/PI3K/Akt pathway; these effects occur independently of the insulin receptor. This function of SNCA represents a new mechanistic insight that creates novel avenues of research with respect to the process of glucose regulation. 相似文献
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36.
GlcNAcylation of histone H2B facilitates its monoubiquitination 总被引:1,自引:0,他引:1
Fujiki R Hashiba W Sekine H Yokoyama A Chikanishi T Ito S Imai Y Kim J He HH Igarashi K Kanno J Ohtake F Kitagawa H Roeder RG Brown M Kato S 《Nature》2011,480(7378):557-560
37.
Tirichine L Imaizumi-Anraku H Yoshida S Murakami Y Madsen LH Miwa H Nakagawa T Sandal N Albrektsen AS Kawaguchi M Downie A Sato S Tabata S Kouchi H Parniske M Kawasaki S Stougaard J 《Nature》2006,441(7097):1153-1156
Induced development of a new plant organ in response to rhizobia is the most prominent manifestation of legume root-nodule symbiosis with nitrogen-fixing bacteria. Here we show that the complex root-nodule organogenic programme can be genetically deregulated to trigger de novo nodule formation in the absence of rhizobia or exogenous rhizobial signals. In an ethylmethane sulphonate-induced snf1 (spontaneous nodule formation) mutant of Lotus japonicus, a single amino-acid replacement in a Ca2+/calmodulin-dependent protein kinase (CCaMK) is sufficient to turn fully differentiated root cortical cells into meristematic founder cells of root nodule primordia. These spontaneous nodules are genuine nodules with an ontogeny similar to that of rhizobial-induced root nodules, corroborating previous physiological studies. Using two receptor-deficient genetic backgrounds we provide evidence for a developmentally integrated spontaneous nodulation process that is independent of lipochitin-oligosaccharide signal perception and oscillations in Ca2+ second messenger levels. Our results reveal a key regulatory position of CCaMK upstream of all components required for cell-cycle activation, and a phenotypically divergent series of mutant alleles demonstrates positive and negative regulation of the process. 相似文献